This research study uses a drug called cyclophosphamide to decrease the incidence of GVHD in matched sibling hematopoietic stem cell transplant. In doing so, the goal of the study is to increase overall survival.

This research protocol has been developed for patients undergoing matched-sibling hematopoietic stem cell transplant (HSCT). The patients who are treated according to this 2 step allogeneic HSCT protocol will receive cyclophosphamide to induce in-vivo tolerization of both autologous and allogeneic lymphocytes, followed by an allogeneic CD34-selected HSCT. The primary research questions relate to immune reconstitution, incidence of GVHD, and relapse in patients who receive lymphocyte treatment of this type in allogeneic HSCT and how it impacts overall survival.

Inclusion Criteria:

1. Any patient with a hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied. Patients will be considered high-risk if they have any of the following:

   1. Age > 50 years
   2. ECOG Performance status of <2
   3. Acute leukemia: requiring more than one chemotherapy regimen to obtain 1st CR; second or greater CR, 1st relapse; any ph+ ALL
   4. CML 2nd chronic phase, accelerated phase, or blastic phase
   5. MDS with IPS of Intermediate 2 or greater
   6. Any myeloproliferative disorder
   7. Hodgkin lymphoma: relapsed, refractory, or primary induction failure
   8. Non-Hodgkin lymphoma: relapsed, refractory, primary treatment failure, or not eligible for an autologous HSCT
   9. Other conditions not listed will be assessed as high-risk by the PI

2. Patients must have a related donor who is either HLA-identical or a one antigen mismatch at the HLA- A; B; C; and DR loci.

3. Patients must adequate organ function:

   1. LVEF of >45%
   2. DLCO (adjusted for hemoglobin) >45% of predicted
   3. Adequate liver function as defined by a serum bilirubin <1.8, AST or ALT < 2.5X upper limit of normal
   4. Creatinine clearance of > 60 ml/min

4. Patients must be willing to use contraception if they have childbearing potential

5. Able to give informed consent

Exclusion Criteria:

1. ECOG performance status of 3 or 4.
2. HIV positive
3. Active involvement of the central nervous system with malignancy
4. Psychiatric disorder that would preclude patients from signing an informed consent
5. Pregnancy
6. Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder.